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Due to the vital role of empathy in promoting prosocial behaviors and nurturing social bonds, there is a growing interest in cultivating empathy. Yet, the effectiveness of existing training methods on empathy, especially on different dimensions of empathy (i.e., affective, cognitive, motivational, and behavioral empathy), varies tremendously, and the underlying causes for this heterogeneity remain insufficiently explored. To address this issue, we categorized various training methods into three distinct approaches based on the premise that empathy can be influenced by factors associated with the subject, the object, and their relationship. Respectively, these are Subject-Oriented, Object-Oriented, and Socially Oriented approaches. To examine the effects of training and sustainability of these approaches on different dimensions of empathy, we conducted a meta-analysis encompassing 110 eligible studies with 32, 44, 39, 39, and 91 samples for affective, cognitive, motivational, behavioral, and composite empathy, respectively. Results showed that trainings produced small and unsustainable effects on affective empathy, moderate and unsustainable effects on cognitive empathy, small and sustainable effects on motivational empathy, and moderate and sustainable effects on behavioral empathy. The effects of training on composite empathy were robust but decreased over time. Among the three training approaches, Socially Oriented approaches were the most effective in improving all dimensions of empathy. Subject-Oriented and Object-Oriented approaches were effective only in improving cognitive and composite empathy. Altogether, our study offers practical guidance for selecting appropriate training approaches and proposes theoretical principles for developing optimal training strategies in both basic research and clinical applications. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Significance Statement: Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with the disorder and 23,224 controls. They identified a rare variant in the gene encoding vascular endothelial growth factor A (VEGFA) that was significantly associated with a two-fold increased risk of IgA nephropathy, which was further confirmed by sequencing analysis. They also identified a novel common variant in PKD1L3 that was significantly associated with lower haptoglobin protein levels. This study, which was well-powered to detect low-frequency variants with moderate to large effect sizes, helps expand our understanding of the genetic basis of IgA nephropathy susceptibility., Background: Genome-wide association studies have identified nearly 20 susceptibility loci for IgA nephropathy. However, most nonsynonymous coding variants, particularly those occurring rarely or at a low frequency, have not been well investigated., Methods: We performed a three-stage exome chip-based association study of coding variants in 8529 patients with IgA nephropathy and 23,224 controls, all of Han Chinese ancestry. Sequencing analysis was conducted to investigate rare coding variants that were not covered by the exome chip. We used molecular dynamic simulation to characterize the effects of mutations of VEGFA on the protein's structure and function. We also explored the relationship between the identified variants and the risk of disease progression., Results: We discovered a novel rare nonsynonymous risk variant in VEGFA (odds ratio, 1.97; 95% confidence interval [95% CI], 1.61 to 2.41; P = 3.61×10 -11 ). Further sequencing of VEGFA revealed twice as many carriers of other rare variants in 2148 cases compared with 2732 controls. We also identified a common nonsynonymous risk variant in PKD1L3 (odds ratio, 1.16; 95% CI, 1.11 to 1.21; P = 1.43×10 -11 ), which was associated with lower haptoglobin protein levels. The rare VEGFA mutation could cause a conformational change and increase the binding affinity of VEGFA to its receptors. Furthermore, this variant was associated with the increased risk of kidney disease progression in IgA nephropathy (hazard ratio, 2.99; 95% CI, 1.09 to 8.21; P = 0.03)., Conclusions: Our study identified two novel risk variants for IgA nephropathy in VEGFA and PKD1L3 and helps expand our understanding of the genetic basis of IgA nephropathy susceptibility., (Copyright © 2023 by the American Society of Nephrology.)

One-carbon homologation reactions based on one-carbon insertion into the N-O bond of heterocycles have received tremendous interest over the past decades. However, these protocols have to rely on the use of hazardous and not easily accessible diazo compounds as precursors, and examples of the relevant asymmetric catalysis have not been reported. Here we show that a copper-catalyzed intermolecular formal (5 + 1) annulation of 1,5-diynes with 1,2,5-oxadiazoles involving one-carbon insertion into the heterocyclic N-O bond via non-diazo approach. This method enables practical and atom-economic synthesis of valuable pyrrole-substituted oxadiazines in generally moderate to good yields under mild reaction conditions. In addition, the possibility of such an asymmetric formal (5 + 1) annulation also emerges., (© 2023. Springer Nature Limited.)

Long-term dance training offers numerous benefits, including improvements in physical health, posture, body coordination, and mental health and well-being. Since dance is an art form of body-to-body communication, professional dancers may share feelings and thoughts on dance with their partners, owing to their shared training experiences. Considering this perspective, one may expect that professional dancers would demonstrate pronounced neural similarities when viewing dancing videos, which could be associated with their training duration. To test these hypotheses, we collected functional magnetic resonance imaging (fMRI) data while presenting ballroom dancing and neutral video clips with long durations (∼100 s each) to 41 professional ballroom dancers (19 pairs of dance partners) and 39 age- and sex-matched nondancers. Our findings revealed that dancers exhibited broader and stronger neural similarities across the whole brain when watching dancing video clips, as compared to the control group. These increased neural similarities could be interpreted in at least two distinct ways. First, neural similarities in certain brain regions within the motor control circuit (i.e., frontal cortical-basal ganglia-thalamic circuit) were significantly correlated with dance-related information (e.g., dance partners' cooperation duration), which reinforced the impact of long-term dance training on neural synchronization. Second, neural similarities in other brain regions (e.g., memory-related brain regions) were significantly correlated with subjects' impression of the viewed videos (i.e., whether they have watched before, familiarity, and liking), which may not necessarily be directly linked to long-term dance training. Altogether, our study provided solid evidence for synchronized neural mechanisms in professional dancers due to long-term dance training., Competing Interests: Declaration of Competing Interest The authors declare no commercial or financial conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

DNA sensors play crucial roles in inflammation and have been indicated to be involved in antitumor or tumorigenesis, while it is still unclear whether DNA sensors have potential roles in the prognosis and immunotherapy of hepatocellular carcinoma (HCC). Herein, The Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze RNA sequencing data and clinical information. A total of 14 DNA sensors were collected and performed consensus clustering to determine their molecular mechanisms in HCC. Two distinct molecular subtypes (Clusters C1 and C2) were identified and were associated with different overall survival (OS). Immune subtype analysis revealed that C1 was mainly characterized by inflammation, while C2 was characterized by lymphocyte depletion. Immune scoring and immunomodulatory function analysis confirmed the different immune microenvironment of C1 and C2. Notably, significant differences in "Hot Tumor" Immunophenotype were observed between the two subtypes. Moreover, the prognostic model based on DNA sensors is capable of effectively predicting the OS of HCC patients. Besides, the chemotherapeutic drug analysis showed the different sensitivity of two subtypes. Taken together, our study shows that the proposed DNA sensors were a reliable signature to predict the prognosis and immunotherapy response with potential application in the clinical decision and treatment of HCC.

Neural indicators of pain discriminability have far-reaching theoretical and clinical implications but have been largely overlooked previously. Here, to directly identify the neural basis of pain discriminability, we apply signal detection theory to three EEG (Datasets 1-3, total N = 366) and two fMRI (Datasets 4-5, total N = 399) datasets where participants receive transient stimuli of four sensory modalities (pain, touch, audition, and vision) and two intensities (high and low) and report perceptual ratings. Datasets 1 and 4 are used for exploration and others for validation. We find that most pain-evoked EEG and fMRI brain responses robustly encode pain discriminability, which is well replicated in validation datasets. The neural indicators are also pain selective since they cannot track tactile, auditory, or visual discriminability, even though perceptual ratings and sensory discriminability are well matched between modalities. Overall, we provide compelling evidence that pain-evoked brain responses can serve as replicable and selective neural indicators of pain discriminability., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Renal inflammation is an initial pathological process during progressive renal injury regardless of the initial cause. Macrophage migration inhibitory factor (MIF) is a truly proinflammatory stress mediator that is highly expressed in a variety of both inflammatory cells and intrinsic kidney cells. MIF is released from the diseased kidney immediately upon stimulation to trigger renal inflammation by activating macrophages and T cells, and promoting the production of proinflammatory cytokines, chemokines, and stress molecules via signaling pathways involving the CD74/CD44 and chemokine receptors CXCR2, CXCR4, and CXCR7 signaling. In addition, MIF can function as a stress molecule to counter-regulate the immunosuppressive effect of glucocorticoid in renal inflammation. Given the critical position of MIF in the upstream inflammatory cascade, this review focuses on the regulatory role and molecular mechanisms of MIF in kidney diseases. The therapeutic potential of targeting MIF signaling to treat kidney diseases is also discussed.

Migraine without aura (MWoA) is a major neurological disorder with unsatisfactory adherence to current medications. Acupuncture has emerged as a promising method for treating MWoA. However, the brain mechanism underlying acupuncture is yet unclear. The present study aimed to examine the effects of acupuncture in regulating brain connectivity of the key regions in pain modulation. In this study, MWoA patients were recruited and randomly assigned to 4 weeks of real or sham acupuncture. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. A modern neuroimaging literature meta-analysis of 515 fMRI studies was conducted to identify pain modulation-related key regions as regions of interest (ROIs). Seed-to-voxel resting state-functional connectivity (rsFC) method and repeated-measures two-way analysis of variance were conducted to determine the interaction effects between the two groups and time (baseline and post-treatment). The changes in rsFC were evaluated between baseline and post-treatment in real and sham acupuncture groups, respectively. Clinical data at baseline and post-treatment were also recorded in order to determine between-group differences in clinical outcomes as well as correlations between rsFC changes and clinical effects. 40 subjects were involved in the final analysis. The current study demonstrated significant improvement in real acupuncture vs sham acupuncture on headache severity (monthly migraine days), headache impact (6-item Headache Impact Test), and health-related quality of life (Migraine-Specific Quality of Life Questionnaire). Five pain modulation-related key regions, including the right amygdala (AMYG), left insula (INS), left medial orbital superior frontal gyrus (PFCventmed), left middle occipital gyrus (MOG), and right middle cingulate cortex (MCC), were selected based on the meta-analysis on brain imaging studies. This study found that 1) after acupuncture treatment, migraine patients of the real acupuncture group showed significantly enhanced connectivity in the right AMYG/MCC-left MTG and the right MCC-right superior temporal gyrus (STG) compared to that of the sham acupuncture group; 2) negative correlations were established between clinical effects and increased rsFC in the right AMYG/MCC-left MTG; 3) baseline right AMYG-left MTG rsFC predicts monthly migraine days reduction after treatment. The current results suggested that acupuncture may concurrently regulate the rsFC of two pain modulation regions in the AMYG and MCC. MTG and STG may be the key nodes linked to multisensory processing of pain modulation in migraine with acupuncture treatment. These findings highlighted the potential of acupuncture for migraine management and the mechanisms underlying the modulation effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Nicotine is the main addictive component in cigarettes that motivates dependence on tobacco use for smokers and makes it difficult to quit through regulating a variety of neurotransmitter release and receptor activations in the brain. Even though nicotine has an analgesic effect, clinical studies demonstrated that nicotine abstinence reduces pain threshold and increases pain sensitivity in smoking individuals. The demand for opioid analgesics in nicotine abstinent patients undergoing surgery has greatly increased, which results in many side effects, such as nausea, vomiting, and respiratory depression, etc. In addition, these side effects would hinder patients' physical and psychological recovery. Therefore, identifying the neural mechanism of the increase of pain sensitivity induced by nicotine abstinence and deriving a way to cope with the increased demand for postoperative analgesics would have enormous basic and clinical implications. In this review, we first discussed different experimental pain stimuli (e.g., cold, heat, and mechanical pain)-induced pain sensitivity changes after a period of nicotine dependence/abstinence from both animal and human studies. Then, we summarized the effects of the brain neurotransmitter release (e.g., serotonin, norepinephrine, endogenous opioids, dopamine, and γ-aminobutyric acid) and their corresponding receptor activation changes after nicotine abstinence on pain sensitivity. Finally, we discussed the limits in recent studies. We proposed that more attention should be paid to human studies, especially studies among chronic pain patients, and functional magnetic resonance imaging might be a useful tool to reveal the mechanisms of abstinence-induced pain sensitivity changes. Besides, considering the influence of duration of nicotine dependence/abstinence and gender on pain sensitivity, we proposed that the effects of nicotine abstinence and individual differences (e.g., duration of abstinence from smoking, chronic/acute abstinence, and gender) on abstinence-induced pain sensitivity should be fully considered in formulating pain treatment protocols. In summary, this paper could deepen our understanding of nicotine abstinence-induced pain sensitivity changes and its underlying neural mechanism, and could also provide effective scientific theories to guide clinical pain diagnosis and treatment, which has important clinical significance.

Spinal cord magnetic resonance imaging (MRI) is an advanced imaging technique (mainly in the cervical cord) and has been gradually used in basic scientific research such as human sensation and motor function, and clinical applications such as spinal cord injury, myelitis, and chronic pain, etc. The development of spinal cord MRI is still at the early stage compared with brain MRI and limited by the current MRI technology and data analysis methods. This review focuses on the methods and applications of spinal cord MRI technology in the basic research fields of cognitive neuroscience and clinical application. Firstly, we will introduce the imaging principle, methods, measurement standards, and applications of most commonly used multimodal spinal cord MRI techniques, including quantitative spinal cord MRI (such as structural, diffusion, spectroscopy, myelin water, magnetization transfer, and chemical exchange saturation transfer imaging, etc.) and spinal functional MRI (fMRI). Secondly, we will discuss the technical challenges and possible solutions of spinal cord MRI data processing from the three dimensions of denoising, data processing pipeline optimization, and repeatability and reliability. Finally, we will discuss the application status and development prospects of spinal cord MRI.

Pain inhibition by additional somatosensory input is the rationale for the widespread use of Transcutaneous Electrical Nerve Stimulation (TENS) to relieve pain. Two main types of TENS produce analgesia in animal models: high-frequency (∼50-100 Hz) and low-intensity 'conventional' TENS, and low-frequency (∼2-4 Hz) and high-intensity 'acupuncture-like' TENS. However, TENS efficacy in human participants is debated, raising the question of whether the analgesic mechanisms identified in animal models are valid in humans. Here, we used a sham-controlled experimental design to clarify the efficacy and the neurobiological effects of 'conventional' and 'acupuncture-like' TENS in 80 human volunteers. To test the analgesic effect of TENS we recorded the perceptual and brain responses elicited by radiant heat laser pulses that activate selectively Aδ and C cutaneous nociceptors. To test whether TENS has a long-lasting effect on brain state we recorded spontaneous electrocortical oscillations. The analgesic effect of 'conventional' TENS was maximal when nociceptive stimuli were delivered homotopically, to the same hand that received the TENS. In contrast, 'acupuncture-like' TENS produced a spatially-diffuse analgesic effect, coupled with long-lasting changes both in the state of the primary sensorimotor cortex (S1/M1) and in the functional connectivity between S1/M1 and the medial prefrontal cortex, a core region in the descending pain inhibitory system. These results demonstrate that 'conventional' and 'acupuncture-like' TENS have different analgesic effects, which are mediated by different neurobiological mechanisms., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the association of plasma level of advanced oxidation protein products (AOPPs) with Framingham risk score in type 2 diabetic patients without vascular diseases., Methdos: This cross-sectional study was conducted among type 2 diabetic patients without vascular diseases recruited from 3 affiliated hospitals of Southern Medical University between March, 2010 and May, 2011, with age- and gender-matched healthy individuals as the control group. The demographic data were collected from all the participants, and the biochemical indexes and plasma levels of AOPPs were examined. The risk of cardiovascular disease in 10 years was assessed for all the participants based on their Framingham risk scores., Results: A total of 112 diabetic patients and 49 healthy subjects were enrolled in this study. The diabetic patients had significantly higher body mass index (BMI), blood glucose, triglyceride, low-density lipoprotein (LDL), plasma AOPPs and Framingham risk score but lower high-density lipoprotein level than the control subjects. Spearman correlation analysis showed that plasma level of AOPPs was positively correlated with the Framingham risk score (r=-0.44, P<0.001), and further multiple linear regression analysis suggested that plasma AOPPs level was independently correlated with the Framingham risk score (β0.305, P<0.001)., Conclusion: Type 2 diabetic patients without vascular diseases have significantly higher plasma levels of AOPPs and are at a greater risk of cardiovascular events in 10 years than healthy individuals. Plasma AOPPs are positively correlated with the Framingham risk score, suggesting the value of plasma AOPPs level in predicting the risk of cardiovascular events in these patients.

Negative energy balance is considered as the pathological basis of energy metabolic disorders in periparturient dairy cows. Serum non-esterified fatty acids (NEFA) are one of the most important indicators of energy balance status. Fibroblast growth factor 21 (FGF21) has been identified as a hepatokine involved in regulation of metabolic adaptations, such as promoting hepatic lipid oxidation and ketogenesis, during energy deprivation. However, the direct effects of NEFA on FGF21 expression and secretion in bovine hepatocytes are not entirely clear. The objective of this study was to investigate the effects of different NEFA concentrations on FGF21 expression and secretion in calf hepatocytes cultured in vitro. NEFA were added to the culture solution at final concentrations of 0.6, 1.2, 1.8 and 2.4 mmol/L. After 24 hr of continuous culture, FGF21 mRNA and protein expression levels in the hepatocytes were determined by real-time PCR and Western blot respectively. FGF21 secretion in the supernatant was determined by enzyme-linked immunosorbent assay (ELISA). The results showed that expression and secretion of FGF21 at 0.6 mmol/L NEFA-treated hepatocytes was higher than that of the control group (p < .05). The FGF21 expression and secretion were similar at 1.2, 1.8 and 2.4 mmol/L NEFA-treated hepatocytes and significantly higher than those observed for controls (p < .01). These data suggest that high concentrations of NEFA significantly promote FGF21 expression and secretion in bovine hepatocytes. In particular, this promotion occurs in a dose-dependent manner and may be involved in the pathological processes of energy metabolism disorders of dairy cows in the peripartum period., (© 2017 Blackwell Verlag GmbH.)

The structure of a pectin network requires both calcium (Ca 2+ ) and boron (B). Ca 2+ is involved in crosslinking pectic polysaccharides and arbitrarily induces the formation of an "egg-box" structure among pectin molecules, while B crosslinks rhamnogalacturonan II (RG-II) side chain A apiosyl residues in primary cell walls to generate a borate-dimeric-rhamnogalacturonan II (dRG-II-B) complex through a boron-bridge bond, leading to the formation of a pectin network. Based on recent studies of dRG-II-B structures, a hypothesis has been proposed suggesting that Ca 2+ is a common component of the dRG-II-B complex. However, no in vivo evidence has addressed whether B affects the stability of Ca 2+ crosslinks. Here, we investigated the L-fucose-deficient dwarf mutant mur1, which was previously shown to require exogenous B treatment for phenotypic reversion. Imbibed Arabidopsis thaliana seeds release hydrated polysaccharides to form a halo of seed mucilage covering the seed surface, which consists of a water-soluble outer layer and an adherent inner layer. Our study of mur1 seed mucilage has revealed that the pectin in the outer layer of mucilage was relocated to the inner layer. Nevertheless, the mur1 inner mucilage was more vulnerable to rough shaking or ethylene diamine tetraacetic acid (EDTA) extraction than that of the wild type. Immunolabeling analysis suggested that dRG-II-B was severely decreased in mur1 inner mucilage. Moreover, non-methylesterified homogalacturonan (HG) exhibited obvious reassembly in the mur1 inner layer compared with the wild type, which may imply a possible connection between dRG-II-B deficiency and pectin network transformation in the seed mucilage. As expected, the concentration of B in the mur1 inner mucilage was reduced, whereas the distribution and concentration of Ca 2+ in the inner mucilage increased significantly, which could be the reason why pectin relocates from the outer mucilage to the inner mucilage. Consequently, the disruption of B bridges appears to result in the extreme sensitivity of the mur1 mucilage pectin complex to EDTA extraction, despite the reinforcement of the pectin network by excessive Ca 2+ . Therefore, we propose a hypothesis that B, in the form of dRG-II-B, works together with Ca 2+ to maintain pectin network crosslinks and ultimately the mucilage ultrastructure in seed mucilage. This work may serve to complement our current understanding of mucilage configuration.

A monoenergetic, isotropic proton source suitable for proton radiography applications has been demonstrated at the National Ignition Facility (NIF). A deuterium and helium-3 gas-filled glass capsule was imploded with 39 kJ of laser energy from 24 of NIF's 192 beams. Spectral, spatial, and temporal measurements of the 15-MeV proton product of the (3)He(d,p)(4)He nuclear reaction reveal a bright (10(10) protons/sphere), monoenergetic (ΔE/E = 4%) spectrum with a compact size (80 μm) and isotropic emission (∼13% proton fluence variation and <0.4% mean energy variation). Simultaneous measurements of products produced by the D(d,p)T and D(d,n)(3)He reactions also show 2 × 10(10) isotropically distributed 3-MeV protons.

Advanced glycation end products (AGEs) are protein-bound uremic toxins and are elevated in patients with the end-stage of renal disease. The present study sought to develop an effective method to remove the circulating AGEs from patients using the combination of hemodialysis (HD) and hemoperfusion (HP). Thirty-six patients undergoing maintenance HD for 3 months were randomly divided into two groups. Patients in Group 1 received HD, followed by the combined HP + HD treatment once, whereas patients in Group 2 were first treated with HP + HD and then they received the HD treatment alone. Patients treated with HD alone did not alter higher levels of serum AGEs. In contrast, patients treated with the combined HP + HD exhibited significantly lower levels of serum AGEs and TNF-α. Results from this study demonstrate that the combination of HD + HP treatment may be an effective and better approach to remove the protein-bound uremic toxins and inflammatory cytokines.

Genetic linkage map is helpful for analysis on heredity of some gene families and map-based gene cloning because of its simple and elegant manifestation. One software is in need to draw a gene physical map, which shows a manner similar to the genetic linkage map, based on the relative physical distance between genes. Although some tools like GBrowse and MapViewer etc. are available to draw gene physical map, there are obvious limitations for them: (1) the data need to be decorated in advance; (2) users can't modify results. Therefore, we developed a bio-assisted mapping software--MapGene2Chrom with PC and web versions, which is based on Perl and SVG languages. The software can be used to draw the corresponding physical map quickly in SVG format based on the input data. It will become a useful tool for drawing gene physical map with the advantages of simple input data format, easily modified output and very good portability.

Purpose: Small cell carcinoma of esophagus (SCEC) is characterized by high malignancy and early metastasis. Although the morbidity of SCEC is very low, few studies of patients with SCEC have been conducted in China, there are no sufficient studies of SCEC conducted and reported in the existing published works, and the choices of treatment remain controversial. In this work, we aim to study the clinical characteristics of SCEC, and explore the corresponding treatment and prognosis through retrospective analysis., Material and Methods: The original articles were identified through the leading digital libraries in China in which the terms "esophagus or esophageal" and "small cell esophageal carcinoma" appeared from 2005 to 2009, 1,176 eligible cases were reviewed for clinical data. Analysis of survival was conducted using the Kaplan-Meier method, and differences were compared using the log-rank test., Results: One thousand one hundred seventy-six eligible cases were analyzed; the median age of patients was 57 years, with a male-to-female ratio of 2.4:1. The number of SCEC accounted for 1.26 % of esophageal cancer treated in the same period. Of the tumors, 89.7 % were located in mid- and lower thoracic esophagus. The average tumor length was 5.4 cm (0.5-17 cm). The median overall survival was 11.1 months for all patients. The 1-, 2-, 3-, and 5-year average overall survival rates of 469 patients was 51.1, 25.5, 13.2, 7.9 %, respectively. The median survival time for LD patients who received systemic treatment was 16.8 m, whereas for those who received local treatment (surgery), the median survival time was 10.1 m; the median survival time for ED patients who received systemic treatment was 7.4 m, compared with 5.8 m for those who received sole treatment (chemotherapy or radiotherapy)., Conclusions: SCEC is a tumor characterized by high malignancy and early metastasis. Although our retrospective analysis cannot provide definitive conclusions on the optimal treatment modality for SCEC, however, our results suggest that systemic treatment combined with surgical resection plays a major role in the therapy of SCEC, systemic therapy may be an effective approach for the treatment of SCEC, and randomized, prospective, multicenter studies are needed to identify optimal treatment modalities for SCEC.

Advanced glycation end-products (AGEs) can induce expression of connective tissue growth factor (CTGF), which seems to promote the development of diabetic nephropathy, but the exact signaling mechanisms that mediate this induction are unknown. Here, AGEs induced CTGF expression in tubular epithelial cells (TECs) that either lacked the TGF-beta1 gene or expressed dominant TGF-beta receptor II, demonstrating independence of TGF-beta. Furthermore, conditional knockout of the gene encoding TGF-beta receptor II from the kidney did not prevent AGE-induced renal expression of CTGF and collagen I. More specific, AGEs induced CTGF expression via the receptor for AGEs-extracellular signal-regulated kinase (RAGE-ERK)/p38 mitogen-activated protein kinase-Smad cross-talk pathway because inhibition of this pathway by several methods (anti-RAGE antibody, specific inhibitors, or dominant negative adenovirus to ERK1/2 and p38) blocked this induction. Overexpressing Smad7 abolished AGE-induced Smad3 phosphorylation and CTGF expression, demonstrating the necessity for activation of Smad signaling in this process. More important, knockdown of either Smad3 or Smad2 demonstrated that Smad3 but not Smad2 is essential for CTGF induction in response to AGEs. In conclusion, AGEs induce tubular CTGF expression via the TGF-beta-independent RAGE-ERK/p38-Smad3 cross-talk pathway. These data suggest that overexpression of Smad7 or targeting Smad3 may have therapeutic potential for diabetic nephropathy.

Objective: To evaluate whether antisense oligonucleotides (ASODN) targeting hTERT mRNA could sensitize human pancreatic cancer cell to gemcitabine in vitro., Methods: hTERT mRNA expression was measured by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Telomerase activity was examined by TRAP, polyacrylamide gel electrophoresis and silver staining. The proliferation capacity and the apoptosis of cancer cells were evaluated by MTT assay and double staining with both Annexin V-FITC and PI., Results: Transient transfection in human pancreatic cancer cell with hTERT ASODN diminished the abundance of hTERT mRNA in a concentration-dependent fashion. And 0.2 micromol/L ASODN decreased the telomerase activity by 0.47-fold in cancer cell. The IC(50) value of gemcitabine in ASODN-transfected cell was (0.8 +/- 0.2) micromol/L while that in oligofectamine-transfected control cell (7.3 +/- 0.9) micromol/L with a statistically significant difference. hTERT ASODN significantlly increased the gemcitabine-induced apoptosis rate in pancreatic cancer cell. The gemcitabine-induced apoptosis rate in ASODN-transfected cell was 60.28% while that in oligofectamine-transfected control cell 17.34%., Conclusion: hTERT antisense oligodeoxynucleotide can increase the sensitivity of pancreatic cancer cell to gemcitabine. The mechanism may be due to the down-regulated expression of hTERT mRNA and telomerase activity.

Objective: To compare the long-term results of procedure for prolapse and hemorrhoids(PPH) and Milligan-Morgan(MM) hemorrhoidectomy in the treatment of third- and fourth-degree hemorrhoids., Methods: Ninety-one patients in PPH group and 120 patients in MM group, treated in our hospital from May 2001 to May 2005, were followed up. All the patients suffered with third- or fourth-degree hemorrhoids. The data including symptoms relief, complication and recurrence were compared between two groups., Results: PPH and MM both significantly relieved bleeding (95.6% vs 92.7%), pain (93.1% vs 94.3%) and prolapse (93.4% vs 93.1%). There were no significant differences between two groups(P >0.05). PPH significantly relieved constipation compared with MM(60.0% vs 32.1%, P <0.05). No significant differences of complete relief rates between PPH group and MM group according to different degrees, types and prolapses of hemorrhoids were found(P >0.05). There were no significant differences in the overall complication rate(14.3% vs 12.7%), recurrence rates(12.1% vs 8.8%) and satisfactory degree (85.1 vs 88.2) between two groups as well., Conclusion: The long-term outcomes of PPH in the treatment of third and fourth-degree hemorrhoids are similar to Milligan-Morgan hemorrhoidectomy.

Using an estrogen-inducible expression XVE (LexA-VP16-Estragon Receptor) system, we have generated approximately 40 000 independent T-DNA insertion lines of Arabidopsis thaliana. Segregation analyses of about 18000 lines indicated that 51.6% of them contain single T-DNA insertions and that the average insertion number is 1.38 copies per line. Mutants displaying a variety of morphological alterations were identified, including those that affect development of roots,hypocotyls, leaves, floral organs and seeds as well as the flowering time.

Objective: To detect plasma brain natriuretic peptide (BNP) changes in hemodialysis patients with chronic renal failure (CRF) and assess the diagnostic value of BNP for cardiac function., Methods: Plasma BNP concentration was measured in 93 hemodialysis patients with CRF and 52 healthy control subjects. In the 93 patients, echocardiographic examinations were performed to determine the relationship between BNP and cardiac function., Results: The median plasma BNP levels in 52 normal controls were 3.35 pg/ml (1.00-9.73 pg/ml), and 146.5 pg/ml (56.2-546.9 pg/ml) and 90.0 pg/ml (18.3-310.5 pg/ml) in 93 patients before and after hemodialysis, respectively, showing significant difference among those 3 groups (P<0.001). The plasma BNP levels in patients with CRF complicated by heart failure (LVEF<50%) before and after hemodialysis were 686.0 pg/ml (334.5-1319.3 pg/ml) and 248.0 pg/ml (80.3-814.5 pg/ml) respectively, significantly higher than 62.8 pg/ml (22.0-321.6 pg/ml) and 20.7 pg/ml (1.0-200.9 pg/ml) in patients with normal cardiac function (LVEF > or = 50%) (P=0.002). The plasma BNP levels in patients with dilated left ventricle before and after hemodialysis were 609.0 pg/ml (254-1152.0 pg/ml) and 310.0 pg/ml (28.3-839.6 pg/ml) respectively, significantly higher than 62.8 pg/ml (23.2-192.5 pg/ml) and 22.4 pg/ml (1.0-80.7 pg/ml) in patients with normal left ventricle. Multiple linear regression analysis for left ventricular diastolic dimension, LVEF and plasma BNP level before hemodialysis showed that high BNP level was significantly correlated with dilated left ventricle and poor cardiac function (P<0.01)., Conclusions: Plasma BNP levels in hemodialysis patients with CRF are significantly higher than those in healthy controls, and are significantly lowered after hemodialysis but still remain higher than the normal level. Plasma BNP levels in hemodialysis patients with dilated left ventricle or heart failure are significantly higher than those in patients with normal left ventricle or cardiac function, and high plasma BNP level is significantly correlated with dilated left ventricle and poor cardiac function.

Objective: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and has been shown to play a role in pathogenesis of atherosclerosis. The aim of this study is to investigate the potential role of MIF in the destabilization of atherosclerotic plaques by stimulation of vascular MMP-1 expression., Methods: MIF and matrix metalloproteinase protein-1 (MMP-1) expression in human atherosclerotic plaques were determined by immunohistochemistry. The functional activity of MIF was examined by its ability to induce MMP-1 expression in vascular smooth muscle cells (VSMCs) in vitro., Results: Two-color immunohistochemistry demonstrated that MIF was strongly upregulated in vulnerable, but not in fibrous plaques. Upregulation of vascular MIF was associated with macrophage accumulation (p<0.01), strong expression of vascular MMP-1 (p<0.001), and collagenolysis in vulnerable atheromatous plaques, but not in the fibrous lesions. Co-expression of MIF and MMP-1 in vulnerable atheromatous plaques appeared to contribute to the weakening of fibrous caps and plaque disruption. The role of MIF in vascular MMP-1 expression was demonstrated by the ability of MIF to directly stimulate VSMCs to express MMP-1 mRNA and protein, and to increase MMP-1 activity in a dose- and time-dependent manner, which was blocked by a neutralizing MIF antibody (p<0.001)., Conclusions: MIF and MMP-1 are markedly upregulated in vulnerable atheromatous plaques and are associated with the weakening of the fibrous cap. The ability of MIF to induce MMP-1 expression and collagenolytic activity in VSMCs suggests that MIF may play a role in the destabilization of human atherosclerotic plaques.

Macrophage migration inhibitory factor (MIF) has been shown to participate in both experimental and human atherogenesis. Expression of MMP-9 has been shown to play a role in the instability of atherosclerotic plaque. Thus, we hypothesize that MIF may participate in the destabilization of atherosclerotic plaques by stimulating MMP-9 expression. This hypothesis was investigated by examining the expression of MIF and MMP-9 in human atherosclerotic plaques using two-color immunostaining and by determining the potential role of MIF in the induction of MMP-9 expression in vascular smooth muscle cells (VSMC) and macrophages in vitro. Two-color immunohistochemistry demonstrated that MIF was strongly upregulated by macrophages and VSMCs. This was associated with marked increase in MMP-9 expression in vulnerable atheromatous plaques, but not in the fibrous lesions. Upregulation of MIF and MMP-9 in vulnerable atheromatous plaques was associated with the weakening of fibrous caps. The role of MIF in MMP-9 expression was demonstrated by the ability of MIF to directly induce MMP-9 mRNA and protein expression in macrophages and in VSMCs in a dose and time-dependent manner, which was blocked by a neutralizing MIF antibody. In conclusion, MIF and MMP-9 are markedly upregulated in vulnerable atheromatous plaques. The ability of MIF to induce MMP-9 expression in VSMCs and macrophages suggests that MIF may play a role in the destabilization of human atherosclerotic plaques.

Objective: To estimate the clinical value of continuous renal replacement therapy (CRRT) in the treatment of severe acute renal failure (ARF) and identify the factors influencing the patients' prognosis., Methods: The clinical characteristics, disease severity and prognosis were retrospectively studied in 116 patients with severe ARF undergoing CRRT from January, 1998 to May, 2004, in comparison with those in 102 such patients treated with intermittent hemodialysis (IHD)., Results: The mean score of Acute Physiology and Chronic Health Evaluation II (APACHE II) was 27.0+/-7.5 in patients receiving CRRT, of whom 56 (48%) had a score no less than 29, 36 (31%) between 24 to 29 and 24 (21%) less than 24. The mean APACHE II score was 21.9+/-5.2 in patients with IHD, and none of them had a score over 29, 44 (43%) had a score between 24 to 29 and 58 (57%) less than 24. The mean APACHE II score of CRRT group was significantly higher than that of IHD group (t=4.769, P=0.000), suggesting that most of the patients treated with CRRT were in critical condition. The patients' survival rate, however, did not differ significantly between the two groups, being 37% (43/116) in CRRT group and 48/ (49/102) in IHD group (X2=2.678, P=0.101 8). When only the patients with a score no less than 24 were compared, the survival rate of CRRT group was significantly higher than that of IHD group (24% vs 9%, X2=4.229, P=0.039 7), demonstrating better effect of CRRT than IHD in the management of critical ARF cases. In patients treated with CRRT, the patients in fatal cases had significantly older age, more critical condition (indicated by APACHE II score) and greater dependence on mechanical ventilation or vasoactive support than those who survived (P<0.05)., Conclusions: CRRT is one of the effective methods for management of severe ARF patients, especially in those with critical conditions, with better effect than that of IHD. The prognosis of severe ARF patients treated with CRRT can be influenced by the patients' age and disease severity, and the need of vasoactive drugs or mechanical ventilation may help predict the patients' prognosis.

Crescentic glomerulonephritis is characterized by glomerular fibrin deposition, and experimental crescentic glomerulonephritis has been shown to be fibrin-dependent. Net fibrin deposition is a balance between activation of the coagulation system causing glomerular fibrin deposition and fibrin removal by the plasminogen-plasmin (fibrinolytic) system. Plasminogen activator inhibitor-1 (PAI-1) inhibits fibrinolysis by inhibiting plasminogen activators and has effects on leukocyte recruitment and matrix deposition. To test the hypothesis that the presence of PAI-1 and its levels were a determinant of injury in crescentic glomerulonephritis, accelerated anti-glomerular basement membrane glomerulonephritis was induced in mice genetically deficient in PAI-1 (PAI-1 -/-), PAI-1 heterozygotes (PAI-1 +/-), and mice engineered to overexpress PAI-1 (PAI-1 tg). Compared with strain-matched genetically normal animals, PAI-1 -/- mice with glomerulonephritis developed fewer glomerular crescents, less glomerular fibrin deposition, fewer infiltrating leukocytes, and less renal collagen accumulation at day 14 of disease. The reduction in disease persisted at day 28, when injury had become more established. In contrast, mice overexpressing the PAI-1 gene (PAI-1 tg), that have basal plasma and renal PAI-1 levels several times, normal developed increased glomerular crescent formation, more glomerular fibrin deposition, increased numbers of infiltrating leukocytes, and more renal collagen at both time points. These studies demonstrate that PAI-1 is a determinant of glomerular fibrin deposition and renal injury in crescentic glomerulonephritis.

Spring wheat Longchun No. 13 and Ganmai No. 8 were introduced by sorghum DNA via pollen tube pathway, and two stable progenies (89,122 and 89,144 respectively) were obtained through selection for several years. The results of photosynthetic analysis showed that photosynthetic rate (P) and photosynthetic/transpiration rate (E/P) of 89,122 and 89,144 were mediated between their recipients and donor respectively, which demonstrated stronger photosynthetic efficiency than their receptors. However, the delta 13 C values in assimilates from 89,122, 89,144 and their maternal wheat cultivars G8 and L13 were approximately same, and they were significant different from sorghum. The chlorophyll content and the ratio of Chla/Chlb of them also showed that wheat cultivars and sorghum were different. It might demonstrated that the stronger photosynthetic efficiency of the progenies was due to their higher Calvin cycle metabolism efficiency rather than their carbon-fixation pathway difference. On the other hand, it also suggested that the distant genetic materials of the sorghum affected the photosynthetic characteristics of 89122 and 89144.